Matsuda Research Group
since 2004

  at Tokyo Institute of Technology  
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Biocatalysis for green chemistry

Our research interest is to promote green chemistry by using biocatalytic reactions; for example, kinetic resolutions of racemic alcohol by lipase using CO2-based solvents, and carboxylation using decarboxylase using CO2 as a substrate or solvent, asymmetric reduction of ketones by alcohol dehydrogenase, etc. Because of homo-chirality in biology on the earth, for instance amino acids which are composed of only left-handed or L-isomer, the discovery and development of stereoselective organic synthetic methods for pharmaceutical and agrochemicals are very important. Chemical and biological catalysts have been developed throughout several decades. To synthesize them in environmentally friendly methods, enzymes are being used as catalysts.

1. Biocatalysis using CO2 for lipase catalyzed reaction

We have utilized pressurized CO2 (liquid or supercritical CO2 ), which has numerous positive impacts on green chemistry, as an excellent platform for biocatalysis. It was found that pressurized CO2 is superior to conventional organic solvents for lipase-catalyzed reactions. We also achieved waste-minimization (E-factor < 0.3) in large-scale biosynthesis of chiral compounds with a continuous reactor using pressurized CO2 fluid. Furthermore, we combined the volume-expansion capability of CO2 with a bio-based liquid into CO2 -expanded bio-based liquids as sustainable and efficient reaction media for biocatalysis. The lipase-catalysed transesterification in this new solvent systems resulted in increased biocatalytic activity, especially with bulky substrates such as rac-1-adamantylethanol. Currently, we are pursuing to elucidate the mechanism of the acceleration in enzymatic reactions caused by CO2 . By these studies of green chemistry using enzyme and pressurized CO2 , we hope to fulfill the role of scientists, to protect the environment for a sustainable future.

2. Biocatalysis using CO2 as a substrate: Carboxylation reaction

Carbon dioxide is an abundant, safe, and inexpensive carbon source. The development of CO2 fixation reactions on organic molecules, carboxylation, is one of the challenges in synthetic chemistry. We succeeded that decarboxylase in the cells of Bacillus megaterium PYR2910 catalyzes the reverse reaction, CO2 fixation (carboxylation), in aqueous supercritical CO2 two layer system. CO2 was fixed on pyrrole to produce pyrrole-2-carboxylate at 10 MPa (about 100 atm). The yield of the reaction in supercritical CO2 was much higher than that at atmospheric pressure.

3. Biocatalytic Baeyer-Villiger oxidation using O2 in air

The Baeyer-Villiger oxidation is an organic reaction used to convert a ketone to an ester. Usually, a peroxyacid (such as mCPBA), which can be explosive, is used, but we use oxygen in air, instead, by using enzyme, peroxidase. We successfully found a unique peroxidase from Microbe Fusarium sp. by the screening of soil using acetone, the smallest ketone, as the only carbon source. Lactones, necessary as fragrances, can be obtained by the reaction of the cyclic ketones. Furthermore, the enzyme is also versatile for the asymmetric oxidation of sulfides to sulfoxides.

4. Biocatalytic oxidation of aldehyde to carboxylic acid

Oxidation reactions are one of the most important reactions organic synthesis. For example, oxidation of aldehyde to carboxylic acid can be conducted easily using chemical reagents. However, it often uses dangerous, toxic, and explosive reagents with a strong oxidation power. To make the reaction safer, we succeeded to use an enzyme, aldehyde dehydrogenase.

5. Biocatalytic asymmetric reduction

We have found that strains of Geotrichum candidum have many robust oxidoreductases with extremely excellent stereoselectivity. The excellent enantioselectivity can be achieved even when very challenging bulky-bulky ketones are used. Moreover, mutation of one key residue located within the substrate binding pocket has expanded the substrate specificity and altered the enantiopreference of this enzyme completely. Investigation of a detailed interaction between mutated residue in the binding pocket and the substrate through structural study will contribute in solving the reaction mechanism of this oxidoreductase and other oxidoreductases in general.


Department of Life Science and Technology
School of Life Science and Technology
Tokyo Institute of Technology

Matsuda Research Group

J3-5 4259 Nagatsuta-cho, Midori-ku, Yokohama, Japan, 226-8501
Tel/Fax: +81 45-924-5757
Office J3-913, Student room J3-914, Experiment rooms J3-915 and 921
E-mail tmatsuda @ delete spaces before and after "@")